Differential Effects of PKC Inhibitors on Gelatinase B and Interleukin 6 Production in the Mouse Macrophage

• Published in: Cytokine (Philadelphia, Pa.) Pa.), 1995-02, Vol.7 (2), p.130-136
• Main Authors: Tremblay, Pierre, Houde, Michel, Arbour, Nathalie, Rochefort, Daniel, Masure, Stefan, Mandeville, Rosemonde, Opdenakker, Ghislain, Oth, Daniel
• Format: Article
• Language: English
• Subjects: Alkaloids - pharmacology; Animals; Biological Assay; Blotting, Northern; Calphostin C/CGP41251/RAW 264.7/Staurosporine; Cell Line, Transformed; Collagenases - analysis; Collagenases - biosynthesis; Gene Expression - drug effects; Interleukin-6 - analysis; Interleukin-6 - biosynthesis; Macrophages - drug effects; Macrophages - immunology; Macrophages - metabolism; Matrix Metalloproteinase 9; Mice; Naphthalenes; Nitric Oxide - biosynthesis; Polycyclic Compounds - pharmacology; Protein Kinase C - antagonists & inhibitors; RNA, Messenger - analysis; RNA, Messenger - biosynthesis; Staurosporine; Tumor Necrosis Factor-alpha - biosynthesis
• ISSN: 1043-4666; 1096-0023
• DOI: 10.1006/cyto.1995.1017

Pretreatment of LPS-induced RAW 264.7 cells with three PKC inhibitors suggests that induction of TNF-α, nitric oxide (NO), gelatinase B (Gel B) and IL-6 involves at least three distinct signalling pathways. We confirmed the PKC dependence of TNF-α and NO productions and found that Gel B was inhibited by Calphostin C (CAL), but potentiated by staurosporine (STAR) and CGP 41 251. IL-6 production was stimulated by the three inhibitors. Our results indicate that up-regulation of Gel B, TNF-α and NO seems to involve PKC at different levels, whereas up-regulation of IL-6 production appears to be PKC-independent. However, IL-6 production in RAW 264.7 cells seems to be down-regulated by a PKC-dependent feedback mechanism.